Single-subject classification of schizophrenia by event-related potentials during selective attention

Executive dysfunction has repeatedly been proposed as a robust and promising substrate of analytical approaches in the research of neurocognitive markers of schizophrenia. Here, we present a mixed model- and data-driven classification approach by applying a task that targets executive dysfunction in schizophrenia and by investigating relevant event-related potential (ERP) features with machine learning classifiers. Forty schizophrenic patients and forty matched healthy controls completed the Attention Network Test while an electroencephalogram was recorded. Target-locked N1 and P3 ERP components were constructed and submitted to different classification analyses without a priori hypotheses. Standardized source localization was applied to estimate neural sources of N1 and P3 deficits in schizophrenia. We obtained a classification accuracy of 79% using only very few ERP components. Central P3 components following compatible and incompatible trials and right parietal N1 latencies averaged across targets and were sufficient for classification. P3 deficits were associated with anterior cingulate cortex dysfunction, while right posterior current density deficits were observed in schizophrenia during the N1 time frame. The data exemplarily show how automated inference may be applied to classify a pathological state in single subjects without prior knowledge of their diagnoses. While classification accuracy may be optimized by application of other executive paradigms, this approach illustrates the potential of machine learning algorithms for the identification of biomarkers that are independent of clinical assessments. Conversely, data suggest a pathophysiological mechanism that includes early visual and late executive deficits during response inhibition in schizophrenia. ► Machine learning algorithms correctly classify 79% of schizophrenia patients utilizing event-related potentials. ► Only four ERP components are necessary for correct classification. ► Source localization indicates causal alterations of anterior cingulate cortex and right posterior cortex in schizophrenia.